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Objective: Idiopathic intracranial hypertension (IIH) is a neurometabolic disease with an increasing incidence. The pathophysiology is unknown, but improvement of diagnosis and management requires discovery of novel biomarkers. Our objective was to identify such candidate biomarkers in IIH, and secondarily, test for associations between identified metabolites and disease severity., Methods: This is a prospective case-control study with collection of cerebrospinal fluid (CSF), serum, and clinical data from new-onset, treatment-naïve patients with IIH (n = 60). Patients were included consecutively from 2 tertiary headache centers in Denmark, and age, sex, and body mass index (BMI) -matched healthy controls (n = 35) were recruited. Clinical data were retrieved at ocular remission (n = 55). Samples were analyzed using non-targeted mass spectrometry., Results: Serum sphingosine 1-phosphate (S1P), adenosine, and glutamate were 0.46-fold (q < 0.0001), 0.25-fold (q = 0.0048), and 0.44-fold (q < 0.0001) lower, respectively, in IIH. CSF stearoyl-lysophosphatidylcholine (LysoPC-18) and 2-palmitoyl-lysophosphatidylcholine (LysoPC-16) were 0.42 (q = 0.0025) and 0.37 (q < 0.001) -fold lower. LysoPC-18 was higher in patients with moderate-severe versus mild papilledema (p = 0.022). LysoPC-18 correlated positively with retinal nerve fiber layer thickness (p = 0.0012, r = 0.42) and inversely with mean deviation on automated perimetry (p = 0.01, r = -0.35). Higher baseline serum S1P (p = 0.018) and lower CSF LysoPC-16 (p = 0.003) were associated with optic nerve atrophy at ocular remission. Pathway analysis suggests dysregulated lipid metabolism and redox disturbances in new-onset IIH., Interpretation: We identify perturbed metabolism in new-onset IIH. S1P and LysoPC-16 demonstrate potential prognostic value due to association with subsequent optic nerve atrophy. This association between specific, differential metabolites and outcome provides substantial evidence for novel biomarkers of clinical significance that should be the focus of further targeted studies. ANN NEUROL 2024;96:595-607., (© 2024 The Author(s). Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Importance: The magnetic resonance imaging (MRI) criteria currently used to diagnose idiopathic intracranial hypertension (IIH) are based on expert opinion and have limited accuracy. Additional neuroimaging signs have been proposed and used with contradictory results; thus, prospective evidence is needed to improve diagnostic accuracy., Objective: To provide evidence-based, accurate MRI signs for IIH diagnosis., Design, Setting, and Participants: This prospective cohort study was conducted from January 2018 to May 2021 with 3 validation cohorts at 2 Danish headache centers and with 3 independent international cohorts. Consecutive patients with suspected IIH were enrolled. Eligibility required the clinical suspicion of IIH, age 18 years or older, and written informed consent. The validation cohorts comprised patients with confirmed IIH from Austria and the US, and patients without IIH from the US. Data analysis was performed from December 2021 to August 2023., Exposure: Standardized diagnostic workup was performed to classify cases according to current criteria, and blinded evaluation of cerebral radiological diagnostics and papilledema was performed., Main Outcomes and Measures: The primary outcomes were MRI signs associated with IIH as assessed by univariate analyses. An MRI score estimating papilledema was calculated using machine learning. Internal validation of associations with lumbar puncture opening pressure and outcome and external validation of accuracy were performed in 3 cohorts., Results: Of 192 eligible patients (185 women [96.4%]; median [IQR] age, 28.0 [23.0-35.0] years), 110 were classified as having IIH, 4 as having probable IIH, and 1 as having suspected IIH without papilledema; 77 did not have IIH and served as controls, with corresponding age, sex, and weight. Papilledema at diagnosis was associated with perioptic subarachnoid space distension (56 patients [68.3%] vs 21 patients [41.2%]), posterior globe flattening (53 patients [66.3%] vs 10 patients [21.3%]), optic nerve disc protrusion (35 patients [30.4%] vs 2 patients [2.3%]), and transverse sinus venous stenosis (75 patients [79.8%] vs 29 patients [46.8%]). The papilledema-estimating MRI score showed optimal balance between sensitivity (49%) and specificity (87%) when 2 of the 3 latter signs were present and was associated with the lumbar puncture opening pressure and ophthalmological outcome. The score showed strong diagnostic accuracy in the external validation cohorts (587 patients; area under the receiver operating characteristic curve, 0.86) and outperformed the current (2013) diagnostic MRI criteria., Conclusions and Relevance: The findings of this cohort study of patients with IIH and controls suggest that an evidence-based MRI score including posterior globe flattening, optic nerve disc protrusion, and transverse sinus stenosis can estimate the presence of papilledema more accurately than the current diagnostic criteria.

Background: Idiopathic intracranial hypertension is a secondary headache disorder potentially causing visual loss. Neurofilament light chain is a candidate, prognostic biomarker, but further studies of neuronal biomarkers are needed. Our objective was to investigate neurofilament light chain in cerebrospinal fluid (cNfL) and plasma (pNfL), amyloid-beta 42 (Aβ-42), total-tau and phosphorylated-tau in cerebrospinal fluid in new-onset idiopathic intracranial hypertension., Methods: Prospective case-control study including new-onset idiopathic intracranial hypertension and age, sex and BMI matched controls. Biomarkers were compared between patients and controls and related to papilledema, visual fields and opening pressure., Results: We included 37 patients and 35 controls. Patients had higher age-adjusted cNfL (1.4 vs. 0.6 pg/mL, p-adjusted < 0.001), pNfL (0.5 vs. 0.3 pg/mL, p-adjusted < 0.001) and total-tau/Aβ-42 (0.12 vs. 0.11, p-adjusted = 0.039). Significant, positive linear correlations were found between cNfL, pNfL, total-tau/Aβ-42 and opening pressure. Patients with severe papilledema had elevated cNfL compared to mild-moderate papilledema (median cNfL: 4.3 pg/mL (3.7) versus 1.0 pg/mL (1.4), p-adjusted = 0.009). cNFL was inversely associated with perimetric mean deviation (r = -0.47, p-adjusted < 0.001)., Conclusions: cNfL, pNfL and total-tau/Aβ-42 were elevated in new-onset idiopathic intracranial hypertension. cNfL was associated with severity of papilledema and visual field defects at diagnosis. This indicates early axonal damage. Neurofilament light chain is a candidate biomarker for disease severity., Competing Interests: Declaration of conflicting interestsThe authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: KS: No conflicts of interest. JJK: Received funding from the Lundbeck Foundation, Rigshospitalet-Glostrup and Odense University Hospital. RHJ: Paid lectures for Pfizer, Eli-Lilly, Merck, TEVA, Novartis, Lundbeck and Allergan. Investigator in clinical trials with Eli-Lilly, Novartis and Lundbeck; Director of Danish Headache Center, Lifting The Global Burden of Headache and Founder of Master of Headache Disorders at University of Copenhagen. Recived research funding from University of Copenhagen, Rigshospitalet, Lundbeck Foundation, The Medical Society in Copenhagen, NovoNordisk Foundation and Tryg Foundation. TP: No conflicts of interest. CSK: No conflicts of interest. SGH: No conflicts of interest. SMH: No conflicts of interest. EAW: Medical Advisory Board for StatuManu ICP ApS. Received research funding from Øjenforeningen (Fight for Sight, Denmark) and the Synoptik Foundation. LDM: No conflicts of interest. DB: Presentations (TEVA, Novartis, Pfizer), Travel Support (Allergan, TEVA, Pfizer, Abbvie), Advisory Boards (Novartis, Lilly, Teva, Lundbeck, Pfizer, Abbvie) and Participations in clinical trials (TEVA, Lundbeck, Novartis, Lilly, Novo Nordic Foundation) outside the submitted work (other headache disorders), receiving grants from Odense University Hospital and Rigshospitalet, University of Copenhagen during the conduction of the work.

Background: Idiopathic intracranial hypertension (IIH) occurs more frequently in obese females of childbearing age. A link between eating disorders and poor outcome has been suggested but remains unproven., Methods: This prospective field study at two tertiary headache centers included patients with clinically suspected IIH after standardized diagnostic work-up. Eating disorders were evaluated using validated questionnaires (EDQs). Primary outcome was the impact of eating disorders on IIH severity and outcome, secondary outcome was the prevalence and type of eating disorders in IIH compared to controls., Results: We screened 326 patients; 143 patients replied to the EDQs and were classified as 'IIH' or 'non-IIH' patients. The demographic profile of EDQ-respondents and non-respondents was similar. Presence of an eating disorder did not impact IIH severity (lumbar puncture opening pressure (p = 0.63), perimetric mean deviation (p = 0.18), papilledema (Frisén grad 1-3; p = 0.53)) nor IIH outcome (optic nerve atrophy (p = 0.6), impaired visual fields (p = 0.18)). Moreover, we found no differences in the prevalence and type of eating disorders when comparing IIH with non-IIH patients (p = 0.09)., Conclusion: Eating disorders did not affect IIH severity or outcome. We found the same prevalence and distribution pattern of eating disorders in IIH and non-IIH patients advocating against a direct link between IIH and eating disorders., Competing Interests: Declaration of conflicting interestsThe authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: T.W.: No conflicts of interest. J.L.: No conflicts of interest. M.B.L.: No conflicts of interest. N.S.H.: Received funding from the Novo Nordic Foundation (NNF20OC0065926) during the conduction of the work and gave lectures for Pfizer, University of Southern Denmark, and University of Copenhagen. J.J.K.: Received funding from the Lundbeck Foundation, Odense University Hospital and Rigshospitalet during the study. L.H.: No conflicts of interest. S.M.H.: Received grants from Fight for Sight, Denmark and the Synoptik Foundation. L.D.M.: No conflicts of interest. R.H.J.: Gave lectures for Pfizer, Eli-Lilly, ATI, Merck, TEVA, Novartis, Lundbeck and Allergan. Investigator in clinical trials with ATI, Eli-Lilly, Novartis and Lundbeck. Director of Danish Headache Center, Lifting The Global Burden of Headache and Founder of Master of Headache Disorders at University of Copenhagen. Recived research funding from University of Copenhagen, Rigshospitalet, ATI, Lundbeck Foundation, The Medical Society in Copenhagen, NovoNordisk Foundation and Tryg Foundation. D.B.: Participated in clinical trials and served with lectures as well as on advisory or speaker boards for Novartis, Eli Lilly, Lundbeck, Pfizer, Abbvie and Teva outside the submitted work (migraine). Received grants from Odense University Hospital and Rigshospitalet, University of Copenhagen during the conduct of the study.

Introduction: Retinal vessel dynamics analysis has proven to be a viable, non-invasive surrogate marker for increased intracranial pressure. We aimed to test this method in patients with suspected idiopathic intracranial hypertension., Methods: Patients with suspected idiopathic intracranial hypertension were prospectively enrolled for hand-held fundus-videography during diagnostic lumbar puncture. After extracting optic disc images, peripapillary arteriole-to-venule-ratios were measured using machine-learning algorithms with manual identification control. A general linear model was applied to arteriole-to-venule-ratios and corresponding lumbar opening pressures to estimate cerebrospinal fluid pressure., Results: Twenty-five patients were included with a significant difference in arteriole-to-venule-ratio between patients with ( n  = 17) and without ( n  = 8) idiopathic intracranial hypertension (0.78 ± 0.10 vs 0.90 ± 0.08, p  = 0.006). Arteriole-to-venule-ratio correlated inversely with lumbar opening pressure (slope regression estimate -0.0043 (95% CI -0.0073 to -0.0023), p  = 0.002) and the association was stronger when lumbar opening pressure exceeded 15 mm Hg (20 cm H 2 O) (slope regression estimate -0.0080 (95% CI -0.0123 to -0.0039), p  < 0.001). Estimated cerebrospinal fluid pressure predicted increased lumbar opening pressure >20 mm Hg (27 cm H 2 O) with 78% sensitivity and 92% specificity (AUC 0.81, p  = 0.02). A stand-alone arteriole-to-venule-ratio measurement predicting lumbar opening pressure >20 mm Hg (27 cm H 2 O) was inferior with a 48% sensitivity and 92% specificity (AUC 0.73, p =  0.002)., Conclusion: Retinal vessel dynamics analysis with the described model for estimating cerebrospinal fluid pressure is a promising non-invasive method with a high sensitivity and specificity for detecting elevated intracranial pressure at follow-up assessments of patients with confirmed idiopathic intracranial hypertension if initial lumbar opening pressure and arteriole-to-venule-ratio data are available.

Background: Based on expert opinion, abducens nerve palsy and a neuroimaging criterion (≥3 neuroimaging signs suggestive of elevated intracranial pressure) were added to the diagnostic criteria for idiopathic intracranial hypertension. Our objective was to validate this., Methods: This prospective study included patients with new-onset idiopathic intracranial hypertension for a standardized work-up: interview, neuro-ophthalmological exam, lumbar puncture, neuroimaging. Neuroimaging was evaluated by a blinded neuroradiologist., Results: We included 157 patients classified as idiopathic intracranial hypertension (56.7%), probable idiopathic intracranial hypertension (1.9%), idiopathic intracranial hypertension without papilledema (idiopathic intracranial hypertension-without papill edema; 0%), suggested idiopathic intracranial hypertension-without papill edema (4.5%), or non-idiopathic intracranial hypertension (36.9%). Moderate suprasellar herniation was more common in idiopathic intracranial hypertension than non-idiopathic intracranial hypertension (71.4% versus 47.4%, p < 0.01), as was perioptic nerve sheath distension (69.8% versus 29.3%, p < 0.001), flattening of the globe (67.1% versus 11.1%, p < 0.001) and transverse sinus stenosis (60.2% versus 18.9%, p < 0.001). Abducens nerve palsy was of no diagnostic significance. Sensitivity of ≥3 neuroimaging signs was 59.5% and specificity was 93.5%., Conclusion: Moderate suprasellar herniation, distension of the perioptic nerve sheath, flattening of the globe and transverse sinus stenosis were associated with idiopathic intracranial hypertension. We propose that idiopathic intracranial hypertension can be defined by two out of three objective findings (papilledema, opening pressure ≥25 cm cerebrospinal fluid and ≥3 neuroimaging signs).

Background: Our objective was to assess optic nerve sheath diameter (a marker of elevated intracranial pressure) and optic disc elevation (a marker of papilledema) in pseudotumor cerebri syndrome using transorbital sonography., Methods: The study was a prospective case-control study. We included patients with new-onset pseudotumor cerebri syndrome and matched healthy controls. All had fundoscopy, lumbar puncture with opening pressure and transorbital sonography. Sonography was assessed by a blinded observer., Results: We evaluated 45 patients and included 23 cases. We recruited 35 controls. Optic nerve sheath diameter was larger in pseudotumor cerebri syndrome compared to controls (6.3 ± 0.9 mm versus 5.0 ± 0.5 mm, p < 0.001) and so was optic disc elevation (0.9 ± 0.4 mm versus 0.4 ± 0.1 mm, p < 0.001). The optimal cut-off point for optic nerve sheath diameter was 6 mm with a sensitivity of 74% for prediction of pseudotumor cerebri syndrome and 68% for prediction of elevated opening pressure. Specificity was 94%. The optimal cut-off point for optic disc elevation was 0.6 mm. Sensitivity was 100% and specificity 83% for prediction of pseudotumor cerebri syndrome., Conclusion: Optic disc elevation and optic nerve sheath diameter are increased in new-onset pseudotumor cerebri syndrome. Optic disc elevation achieved high specificity and excellent sensitivity for diagnosis of pseudotumor cerebri syndrome. Transorbital sonography (TOS) is a potential, non-invasive screening tool for pseudotumor cerebri syndrome in headache clinics.

Background and Objectives: Psychiatric disease is a frequent comorbidity in idiopathic intracranial hypertension (IIH) and has been associated with a poor subjective outcome. No prospective studies have investigated psychiatric comorbidities in new-onset IIH. Our primary aim was to investigate disease severity in IIH depending on comorbid psychiatric disease. Important secondary outcomes were disease severity after 6 months and prevalence of psychiatric diseases in IIH., Methods: This prospective, observational cohort study consecutively included patients with clinically suspected, new-onset IIH from 2 headache centers. A standardized diagnostic workup was completed to confirm or exclude IIH according to the revised Friedman criteria: semi-structured interview, neurologic and neuro-ophthalmologic examination, lumbar puncture with opening pressure (OP), and neuroimaging. Exclusion criteria were known IIH, secondary intracranial hypertension, missing data, and pregnancy. Disease severity was evaluated based on papilledema, visual fields, OP, and headache in patients with IIH without psychiatric disease (IIH-P) compared with patients with IIH with psychiatric disease (IIH+P). A blinded neuro-ophthalmologist assessed visual outcomes. Age- and sex-matched prevalence rates of psychiatric diseases in the general population were found in national reports., Results: A total of 258 patients were screened; 69 were excluded. A total of 189 patients with clinically suspected IIH were then evaluated with the diagnostic workup and IIH was confirmed in 111 patients (58.7%). A total of 45% of patients with IIH had a psychiatric comorbidity. Visual fields were worse in patients with IIH+P at baseline (-8.0 vs -6.0 dB; p = 0.04) and after 6 months (-5.5 vs -4.0 dB; p < 0.01) compared with IIH-P. Highly prevalent psychiatric disorders were major depressive disorder (24.3%; n = 27), anxiety or stress-related disorders (24.3%; n = 27), and emotionally unstable personality disorder (6.3%; n = 7). Substance abuse (1.8%), schizophrenia (0.9%), and bipolar disorder (0.9%) were rare. In the general population, prevalence estimates of major depressive disorder and emotionally unstable personality disorder were 1.8%-3.3% and 2%, respectively., Discussion: Visual fields were significantly worse at baseline and 6 months in IIH+P compared with IIH-P. Psychiatric comorbidities, particularly depression and emotionally unstable personality disorder, were highly prevalent in IIH. Increased awareness of psychiatric disease as a marker for worse visual status may improve patient care., (© 2022 American Academy of Neurology.)

Elevated intracranial pressure (ICP) is observed in many brain disorders. Obesity has been linked to ICP pathogenesis in disorders such as idiopathic intracranial pressure (IIH). We investigated the effect of diet induced obesity (DIO) on ICP and clinically relevant sequelae. Rats were fed either a control or high fat diet. Following weight gain long term ICP, headache behavior, body composition and retinal outcome were examined. Post-hoc analysis of retinal histology and molecular analysis of choroid plexus and trigeminal ganglion (TG) were performed. DIO rats demonstrated raised ICP by 55% which correlated with the abdominal fat percentage and increased non-respiratory slow waves, suggestive of altered cerebral compliance. Concurrently, DIO rats demonstrated a specific cephalic cutaneous allodynia which negatively correlated with the abdominal fat percentage. This sensitivity was associated with increased expression of headache markers in TG. Additionally, DIO rats had increased retinal nerve fiber layer thickness in vivo associated with raised ICP with a subsequent post-hoc demonstration of neuroretinal degeneration. This study demonstrates for the first time that DIO leads to raised ICP and subsequent clinically relevant symptom development. This novel model of non-traumatic raised ICP could expand the knowledge regarding disorders with elevated ICP such as IIH., (© 2022. The Author(s).)

Background: The kaolin induced obstructive hydrocephalus (OHC) model is well known for its ability to increase intracranial pressure (ICP) in experimental animals. Papilledema (PE) which is a predominant hallmark of elevated ICP in the clinic has not yet been studied in this model using high-resolution digital fundus microscopy. Further, the long-term effect on ICP and optic nerve head changes have not been fully demonstrated. In this study we aimed to monitor epidural ICP after induction of OHC and to examine changes in the optic disc. In addition, we validated epidural ICP to intraventricular ICP in this disease model., Method: Thirteen male Sprague-Dawley rats received an injection into the cisterna magna containing either kaolin-Ringer's lactate suspension (n = 8) or an equal amount of Ringer's lactate solution (n = 5). Epidural ICP was recorded post-operatively, and then continuously overnight and followed up after 1 week. The final epidural ICP value after 1 week was confirmed with simultaneous ventricular ICP measurement. Optic disc photos (ODP) were obtained preoperatively at baseline and after one week and were assessed for papilledema., Results: All animals injected with kaolin developed OHC and had significant higher epidural ICP (15.49 ± 2.47 mmHg) compared to control animals (5.81 ± 1.33 mmHg) on day 1 (p < 0.0001). After 1 week, the epidural ICP values were subsided to normal range in hydrocephalus animals and there was no significant difference in epidural ICP between the groups. Epidural ICP after 1 week correlated with the ventricular ICP with a Pearson's r = 0.89 (p < 0.0001). ODPs from both groups showed no signs of acute papilledema, but 5 out of 8 (62.5%) of the hydrocephalus animals were identified with peripapillary changes., Conclusions: We demonstrated that the raised ICP at day 1 in the hydrocephalus animals was completely normalized within 1 week and that epidural ICP measurements are valid method in this model. No acute papilledema was identified in the hydrocephalus animals, but the peripapillary changes indicate a potential gliosis formation or an early state of a growing papilledema in the context of lateral ventricle dilation and increased ICP., (© 2022. The Author(s).)

Loss of vision is a feared consequence of idiopathic intracranial hypertension (IIH). Optic nerve sheath fenestration (ONSF) may be an effective surgical approach to protect visual function in medically refractory IIH. In this study, we evaluate the impact of unilateral superomedial transconjunctival ONSF on bilateral visual outcome using a comprehensive follow-up program. A retrospective chart review of IIH patients who underwent unilateral ONSF between January 2016 and March 2021 was conducted. Patients fulfilling the revised Friedman criteria for IIH and who had exclusively received ONSF as a surgical treatment were included. Main outcomes were visual acuity (VA); perimetric mean deviation (PMD); papilledema grade; and optic nerve head elevation (maxONHE) 1 week, 2 weeks, and 1, 3, and 6 months after surgery. VA ( p < 0.05), PMD ( p < 0.05), papilledema grade ( p < 0.01), and maxOHNE ( p < 0.001) were improved after 6 months on both the operated and non-operated eye. Prolonged surgical delay impedes PMD improvement (r = -0.78, p < 0.01), and an increasing opening pressure initiates a greater ganglion cell loss (r = -0.79, p < 0.01). In this small case series, we demonstrate that unilateral superonasal transconjunctival ONSF is a safe procedure with an effect on both eyes. Optic nerve head elevation and PMD are feasible biomarkers for assessing early treatment efficacy after ONSF.

Background: Damage of the optic nerve is the major complication of idiopathic intracranial hypertension. A biomarker indicative for optic nerve damage would help identifying high-risk patients requiring surgical procedures. Here, we studied the potential of cerebrospinal fluid neurofilament to predict idiopathic intracranial hypertension-induced optic nerve damage., Methods: In two centers, serum and cerebrospinal fluid of 61 patients with clinically suspected idiopathic intracranial hypertension were prospectively collected. Neurofilament concentrations were measured and related to ophthalmological assessment., Results: The average cerebrospinal fluid neurofilament concentration in patients with moderate and severe papilledema was increased compared to patients with minor and no papilledema (1755 ± 3507 pg/ml vs. 244 ± 102 pg/ml; p  < 0.001). Cerebrospinal fluid neurofilament concentrations correlated with the maximal lumbar puncture opening pressure (r = 0.67, p  < 0.001). In patients fulfilling the Friedman criteria for idiopathic intracranial hypertension with or without papilledema (n = 35), development of bilateral visual field defects and bilateral atrophy of the optic nerve were associated with increased average age-adjusted cerebrospinal fluid neurofilament concentrations. At last follow-up (n = 30), 8/13 of patients with increased, but only 3/17 with normal, cerebrospinal fluid neurofilament had developed bilateral visual field defects and/or bilateral optic nerve atrophy resulting in a sensitivity of 72.7% and a specificity of 73.7% of cerebrospinal fluid neurofilament to detect permanent optic nerve damage., Conclusions: Cerebrospinal fluid neurofilament is a putative biomarker for optical nerve damage in idiopathic intracranial hypertension.

Background: Sufficient pain control and rapid mobilisation after VATS are important to enhance recovery and prevent complications. Thoracic epidural analgesia (TEA) is the gold standard, but failure rates of 9-30% have been described. In addition, TEA reduces patient mobilisation and bladder function. Subpleural continuous analgesia (SCA) is a regional analgesic technique that is placed under direct thoracoscopic vision and is not associated with the mentioned disadvantages of TEA. The objective of this study was to assess surgical feasibility, pain control and patient satisfaction of SCA., Methods: Observational pilot study in patients who underwent VATS pulmonary resection and received SCA (n = 23). Pain scores (numeric rating scale 0-10) and patient satisfaction (5-point Likert scale) were collected on postoperative day (POD) 0-3. Secondary outcomes were the period of urinary catheter use and period to full mobilisation., Results: Placement of the subpleural catheter took an average of 11 min (SD 5) and was successful in all patients. Pain scores on POD 0-3 were 1.2 (SD 1.2), 2.0 (SD 1.9), 1.7 (SD 1.5) and 1.2 (SD 1.1) respectively. On POD 0-3 at least 79% of patients were satisfied or very satisfied on pain relief and mobilisation. The duration of subpleural continuous analgesia was 4 days (IQR 3-5, range 2-11). Urinary catheters were used zero days (IQR 0-1, range 0-6) and full mobilisation was achieved on POD 2 (IQR 1-2, range 1-6)., Conclusion: Subpleural continuous analgesia in VATS pulmonary resection is feasible and provides adequate pain control and good patient satisfaction., Trial Registration: This pilot study was not registered in a trial register.

Anoxic subsurface sediments contain communities of heterotrophic microorganisms that metabolize organic carbon at extraordinarily low rates. In order to assess the mechanisms by which subsurface microorganisms access detrital sedimentary organic matter, we measured kinetics of a range of extracellular peptidases in anoxic sediments of the White Oak River Estuary, NC. Nine distinct peptidase substrates were enzymatically hydrolyzed at all depths. Potential peptidase activities ( V max ) decreased with increasing sediment depth, although V max expressed on a per-cell basis was approximately the same at all depths. Half-saturation constants ( K m ) decreased with depth, indicating peptidases that functioned more efficiently at low substrate concentrations. Potential activities of extracellular peptidases acting on molecules that are enriched in degraded organic matter (d-phenylalanine and l-ornithine) increased relative to enzymes that act on l-phenylalanine, further suggesting microbial community adaptation to access degraded organic matter. Nineteen classes of predicted, exported peptidases were identified in genomic data from the same site, of which genes for class C25 (gingipain-like) peptidases represented more than 40% at each depth. Methionine aminopeptidases, zinc carboxypeptidases, and class S24-like peptidases, which are involved in single-stranded-DNA repair, were also abundant. These results suggest a subsurface heterotrophic microbial community that primarily accesses low-quality detrital organic matter via a diverse suite of well-adapted extracellular enzymes. IMPORTANCE Burial of organic carbon in marine and estuarine sediments represents a long-term sink for atmospheric carbon dioxide. Globally, ∼40% of organic carbon burial occurs in anoxic estuaries and deltaic systems. However, the ultimate controls on the amount of organic matter that is buried in sediments, versus oxidized into CO 2 , are poorly constrained. In this study, we used a combination of enzyme assays and metagenomic analysis to identify how subsurface microbial communities catalyze the first step of proteinaceous organic carbon degradation. Our results show that microbial communities in deeper sediments are adapted to access molecules characteristic of degraded organic matter, suggesting that those heterotrophs are adapted to life in the subsurface., (Copyright © 2019 Steen et al.)

Current therapies for reducing raised intracranial pressure (ICP) under conditions such as idiopathic intracranial hypertension or hydrocephalus have limited efficacy and tolerability. Thus, there is a pressing need to identify alternative drugs. Glucagon-like peptide-1 receptor (GLP-1R) agonists are used to treat diabetes and promote weight loss but have also been shown to affect fluid homeostasis in the kidney. We investigated whether exendin-4, a GLP-1R agonist, is able to modulate cerebrospinal fluid (CSF) secretion at the choroid plexus and subsequently reduce ICP in rats. We used tissue sections and cell cultures to demonstrate expression of GLP-1R in the choroid plexus and its activation by exendin-4, an effect blocked by the GLP-1R antagonist exendin 9-39. Acute treatment with exendin-4 reduced Na + - and K + -dependent adenosine triphosphatase activity, a key regulator of CSF secretion, in cell cultures. Finally, we demonstrated that administration of exendin-4 to female rats with raised ICP (hydrocephalic) resulted in a GLP-1R-mediated reduction in ICP. These findings suggest that GLP-1R agonists can reduce ICP in rodents. Repurposing existing GLP-1R agonist drugs may be a useful therapeutic strategy for treating raised ICP., (Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

Background: It is important to minimize risks associated with live donor nephrectomy. In this study we evaluated the results of left-sided robot-assisted donor nephrectomies in comparison with standard techniques., Methods: Data on perioperative results, kidney function, and recipient and graft survival were collected. All left-sided laparoscopic and hand-assisted procedures were selected as control groups., Results: Fifty-nine robot-assisted procedures were performed by two surgeons. Operative time was significantly longer in the robot-assisted group compared with both control groups. However, it decreased significantly during procedures 40-59 compared with procedures 20-39 (P = 0.014) to median 172.5 (114.0-242.0) min. One conversion to the open approach occurred in the robot group due to a bleeding of the renal artery stump. No difference was found between all techniques at 3 months post-donation., Conclusion: Left-sided robot-assisted donor nephrectomy is feasible with over time a significant decrease in operative time with good outcomes for donor and recipient. Copyright © 2016 John Wiley & Sons, Ltd., (Copyright © 2016 John Wiley & Sons, Ltd.)

Peritoneal dialysis (PD) is an effective treatment for end-stage renal disease. There are several configurations of PD catheter design that may impact catheter function, such as the shape of the intraperitoneal segment, the number of cuffs, and the subcutaneous configuration. This review and meta-analysis was carried out to determine whether there is a clinical advantage for one of the catheter types or configurations. Comprehensive searches were conducted in MEDLINE, Embase, and CENTRAL (the Cochrane Library 2012, issue 10). The methodology was in accordance with the Cochrane Handbook for Interventional Systematic Reviews and written based on the PRISMA statement. The initial search yielded 682 hits from which 13 randomized controlled trials were identified. Outcomes of interest were as follows: catheter survival, drainage dysfunction, migration, leakage, exit-site infections, peritonitis, and catheter removal. Comparing straight vs. swan neck and single vs. double-cuffed catheters, no differences were found when results were pooled. Comparison of straight vs. coiled-tip catheters demonstrated that survival was significantly different in favor of straight catheters (hazard ratio 2.05; confidence interval 1.10-3.79, P=0.02). For surgically inserted catheters, the removal rate and survival at 1 year after insertion were significantly in favor of straight catheters. Our meta-analysis clearly demonstrates benefits for catheters with a straight intraperitoneal segment.

Purpose: Anesthesia information management system (AIMS) technology is designed to facilitate high-quality anesthetic recordkeeping. We examined the hypothesis that no difference exists between AIMS and handwritten anesthetic records in regard to the completeness of important information contained as text data. We also investigated the effect of observational research on the completeness of anesthesiologists' recordkeeping., Methods: As part of a larger randomized controlled trial, participants were randomized to produce 400 anesthetic records, either handwritten (n = 200) or using an AIMS (n = 200). Records were assessed against a 32-item checklist modified from a clinical guideline. Intravenous agent and bolus recordings were quantified, and data were compared between handwritten and AIMS records. Records produced with intensive research observation during the initial phase of the study (n = 200) were compared with records produced with reduced intensity observation during the final phase of the study (n = 200)., Results: The AIMS records were more complete than the handwritten records (mean difference 7.1%; 95% confidence interval [CI] 5.6 to 8.6%; P < 0.0001), with higher completion rates for six individual items on the checklist (P < 0.0001). Drug annotation data were equal between arms. The records completed early in the study, during a period of more intense observation, were more thorough than subsequent records (87.3% vs 81.6%, respectively; mean difference 5.7%; 95% CI 4.2 to 7.3%; P < 0.0001)., Conclusions: The AIMS records were more complete than the handwritten records for 32 predefined items. The potential of observational research to influence professional behaviour in an anesthetic context was confirmed. This trial was registered at the Australian New Zealand Clinical Trials Registry No 12608000068369.

Background: Post-transplantation encapsulating peritoneal sclerosis (EPS) causing bowel obstruction has been identified as a serious complication after kidney transplantation in patients previously treated with peritoneal dialysis. Systemic inflammation and abnormalities on an abdominal computed tomography (CT) scan are important hallmarks of EPS. To our knowledge, this is the first report of a case being diagnosed with late-onset post-transplantation EPS without systemic inflammation or abnormalities on a CT scan which could only be diagnosed by laparotomy., Case Presentation: A 59-year old female presented because of symptoms of bowel obstruction 33 months after kidney transplantation. The patient had a 26-month history of peritoneal dialysis before her first kidney transplantation and was treated with peritoneal dialysis for 4 years before undergoing a second kidney transplantation. Physical examination was unremarkable and laboratory tests showed no signs of systemic inflammation (C-reactive protein <1 mg/L). An abdominal CT scan did not reveal any abnormalities fitting the diagnosis of EPS, except a "feces sign". Given the severity of the progressive symptoms, a diagnostic laparotomy was performed, visualizing a classical EPS. Total peritonectomy and enterolysis were performed, leading to restoration of peristalsis., Conclusion: EPS may occur several years after kidney transplantation in the absence of inflammation and typical radiological abnormalities. Obtaining a diagnosis of post-transplantation EPS is challenging, however, a low threshold for surgical exploration in case of high clinical suspicion and negative findings on the CT scan is mandatory.

Background: Encapsulating peritoneal sclerosis (EPS) is a rare complication of peritoneal dialysis (PD). It is characterized by encapsulation of the bowel, causing symptoms of intestinal obstruction. Exclusive involvement of parts of the bowel may occur and may be more common than previously thought. Our main objective was to investigate and report on patients with localized EPS., Methods: Between July 2002 and December 2011, 9 of 17 EPS patients were referred to our department of surgery for a diagnostic laparotomy. Three of the 9 cases showed localized encapsulation of the small bowel and were selected for the purpose of this study., Results: All 3 patients presented with an acute inflammatory state and symptoms of bowel obstruction. In 2 patients, EPS became clinically overt after kidney transplantation; the third patient was diagnosed while on hemodialysis. All shared a history of PD ranging from 31 to 101 months. In none of the patients was radiologic examination conclusive, although 2 showed peritoneal thickening and ascites. Each patient underwent laparotomy, confirming EPS. In all cases, a thickened peritoneal membrane became apparent, predominantly covering the ileocecal region of the intestine. In addition, a constrictive membrane at the level of the terminal ileum was noted. In 2 cases, the patients underwent enterolysis and dissection of the constricting fibrotic peritoneal membrane (peritonectomy) without bowel resection. The 3rd patient was managed with parenteral nutrition and tamoxifen. The postoperative course in 1 patient was complicated by infected ascites that resolved with antibiotic treatment. Eventually, all patients were doing well, with adequate oral intake and without the need for repeat surgery., Conclusions: Localized EPS may be more common than previously thought. It has a predilection for the level of the terminal ileum. We believe that an elective diagnostic laparotomy should be considered early, because this procedure offers both diagnostic opportunities and therapeutic options. Localized EPS cases may benefit most from enterolysis and peritonectomy.

In this era of organ donor shortage, live kidney donation has been proven to increase the donor pool; however, it is extremely important to make careful decisions in the selection of possible live donors. A body mass index (BMI) above 35 is generally considered as a relative contraindication for donation. To determine whether this is justified, a systematic review and meta-analysis were carried out to compare perioperative outcome of live donor nephrectomy between donors with high and low BMI. A comprehensive literature search was performed in MEDLINE, Embase, and CENTRAL (the Cochrane Library). All aspects of the Preferred Reporting Items for Systematic Reviews and Meta-analyses statement were followed. Of 14 studies reviewed, eight perioperative donor outcome measures were meta-analyzed, and, of these, five were not different between BMI categories. Three found significant differences in favor of low BMI (29.9 and less) donors with significant mean differences in operation duration (16.9 min (confidence interval (CI) 9.1-24.8)), mean difference in rise in serum creatinine (0.05 mg/dl (CI 0.01-0.09)), and risk ratio for conversion (1.69 (CI 1.12-2.56)). Thus, a high body mass index (BMI) alone is no contraindication for live kidney donation regarding short-term outcome.

Background: Peritoneal dialysis is an effective treatment for end-stage renal disease. Key to successful peritoneal dialysis is a well-functioning catheter. The different insertion techniques may be of great importance. Mostly, the standard operative approach is the open technique; however, laparoscopic insertion is increasingly popular. Catheter malfunction is reported up to 35% for the open technique and up to 13% for the laparoscopic technique. However, evidence is lacking to definitely conclude that the laparoscopic approach is to be preferred. This review and meta-analysis was carried out to investigate if one of the techniques is superior to the other., Methods: Comprehensive searches were conducted in MEDLINE, Embase and CENTRAL (the Cochrane Library 2012, issue 10). Reference lists were searched manually. The methodology was in accordance with the Cochrane Handbook for interventional systematic reviews, and written based on the PRISMA-statement., Results: Three randomized controlled trials and eight cohort studies were identified. Nine postoperative outcome measures were meta-analyzed; of these, seven were not different between operation techniques. Based on the meta-analysis, the proportion of migrating catheters was lower (odds ratio (OR) 0.21, confidence interval (CI) 0.07 to 0.63; P = 0.006), and the one-year catheter survival was higher in the laparoscopic group (OR 3.93, CI 1.80 to 8.57; P = 0.0006)., Conclusions: Based on these results there is some evidence in favour of the laparoscopic insertion technique for having a higher one-year catheter survival and less migration, which would be clinically relevant.

Background: Open cholecystectomy (OC) is often preferred over laparoscopic cholecystectomy (LC) in patients with liver cirrhosis and portal hypertension, but evidence is lacking to support this practice. This meta-analysis aimed to clarify which surgical technique is preferable for symptomatic cholecystolithiasis in patients with liver cirrhosis., Methods: A meta-analysis was conducted according to the PRISMA guidelines. Articles published between January 1990 and October 2011 were identified from MEDLINE, Embase and the Cochrane Library. Randomized clinical trials (RCTs) comparing outcomes of OC versus LC for cholecystolithiasis in patients with liver cirrhosis were included. The quality of the RCTs was assessed using the Jadad criteria., Results: Following review of 1422 papers by title and abstract, a meta-analysis was conducted of four RCTs comprising 234 surgical patients. They provided evidence of at least level 2b on the Oxford Level of Evidence Scale, but scored poorly according to the Jadad criteria. Some 97·0 per cent of the patients had Child-Turcotte-Pugh (CTP) grade A or B liver cirrhosis. In all, 96·6 per cent underwent elective surgery. No postoperative deaths were reported. LC was associated with fewer postoperative complications (risk ratio 0·52, 95 per cent confidence interval (c.i.) 0·29 to 0·92; P = 0·03), a shorter hospital stay (mean difference -3·05 (95 per cent c.i. -4·09 to -2·01) days; P < 0·001) and quicker resumption of a normal diet (mean difference -27·48 (-30·96 to -23·99) h; P < 0·001)., Conclusion: Patients with CTP grade A or B liver cirrhosis who undergo LC for symptomatic cholecystolithiasis have fewer overall postoperative complications, a shorter hospital stay and resume a normal diet more quickly than those who undergo OC., (Copyright © 2012 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.)

Background: Peritoneal dialysis (PD) is an effective treatment for end-stage renal disease. It allows patients more freedom to perform daily activities compared to haemodialysis. Key to successful PD is the presence of a well-functioning dialysis catheter. Several complications, such as in- and outflow obstruction, peritonitis, exit-site infections, leakage and migration, can lead to catheter removal and loss of peritoneal access. Currently, different surgical techniques are in practice for PD-catheter placement. The type of insertion technique used may greatly influence the occurrence of complications. In the literature, up to 35% catheter failure has been described when using the open technique and only 13% for the laparoscopic technique. However, a well-designed randomized controlled trial is lacking., Methods/design: The LOCI-trial is a multi-center randomized controlled, single-blind trial (pilot). The study compares the laparoscopic with the open technique for PD catheter insertion. The primary objective is to determine the optimum placement technique in order to minimize the incidence of catheter malfunction at 6 weeks postoperatively. Secondary objectives are to determine the best approach to optimize catheter function and to study the quality of life at 6 months postoperatively comparing the two operative techniques., Discussion: This study will generate evidence on any benefits of laparoscopic versus open PD catheter insertion., Trial Registration: Dutch Trial Register NTR2878.